More than 500,000 U.S. patients have end stage renal disease and over 80% utilize hemodialysis as their renal replacement modality of choice. The Achilles Heel in the care of dialysis patients is the development of a functioning and durable vascular access, preferably an arteriovenous fistula (AVF). The annual cost of treating vascular access dysfunction totals over one billion US dollars. This is largely due to the high proportion of AVFs that fail to mature. After creation, sixty percent of AVFs fail to mature successfully for dialysis use, due to early venous neointimal development and inadequate vasodilation. At present, there are no effective therapies to promote vascular access maturation. Endomimetics has developed a nitric oxide (NO) releasing nanomatrix gel that mimics the characteristic properties of native endothelium. This nanomatrix can be applied on the dialysis AVF at the time of creation. In our Phase I SBIR, the nanomatrix gel demonstrated release of NO over 30 days, inhibited neointimal hyperplasia, and reduced expression of inflammatory markers in a rat AVF model. The Endomimetics nanomatrix gel is a biocompatible peptide based material and minimizes the risk of inflammatory responses. In this Phase II SBIR, we propose to evaluate the efficacy of the nanomatrix gel for AVF maturation at a clinically relevant time point. Aim 1 will include evaluation of gelation properties, ex vivo blood vessel dilation, and assessment of NO effects on inhibition of inflammation. In collaboration with Dr. Lee at the University of Alabama at Birmingham, Aims 2 and 3 will evaluate the efficacy of the Endomimetics nanomatrix gel in an established rodent AVF model, and in a porcine model. Development of the Endomimetics NO releasing nanomatrix gel that promotes AVF maturation may have significant impact in the treatment of patients requiring dialysis. With successful completion of Phase II, we plan to move forward in discussion with the FDA.